Systemic Lupus Erythematosus

The answer first

Systemic lupus erythematosus (SLE) is a chronic, relapsing-remitting autoimmune disease in which loss of immune tolerance drives autoantibody production, immune complex formation and deposition, and multi-organ inflammation. It predominantly affects women of childbearing age (female-to-male ratio about 9 to 1) and runs a highly variable course from mild cutaneous and joint disease to life-threatening renal, neurological or haematological involvement. ^[1]

Three ideas frame everything else on this page: ^[1]

1. SLE is a clinical diagnosis built on a positive ANA plus cumulative weighted criteria. A positive antinuclear antibody (ANA) is the obligatory entry criterion for the 2019 EULAR/ACR classification. From there, the diagnosis rests on accumulating 10 points or more across weighted clinical and immunological domains, after a more likely alternative explanation has been excluded ^[1]. ANA alone never makes the diagnosis; a negative ANA (on a competent immunofluorescence assay) makes classification very unlikely.

2. The two organs that decide prognosis are the kidney and the brain. Lupus nephritis is the strongest predictor of mortality and the commonest route to end-stage kidney disease in SLE. Neuropsychiatric lupus and catastrophic antiphospholipid syndrome are the other major killers. Every patient needs a urinalysis at every visit, and any new neurological symptom in a lupus patient is lupus-related until proven otherwise (after infection is excluded). ^[1]

3. Hydroxychloroquine is the backbone of management for nearly every patient. It reduces flares, improves survival, protects against renal and cutaneous disease, lowers thrombosis risk, and is safe in pregnancy. The LUMINA cohort showed a clear survival benefit ^[2]. Stopping it is almost always the wrong answer.

DWE high-yield: The single most discriminating antibody panel in SLE is anti-dsDNA (sensitive for activity and nephritis, low specificity) and anti-Smith (anti-Sm) (high specificity, low sensitivity). Anti-Sm is the most specific antibody for SLE — its presence essentially confirms the diagnosis. A rising anti-dsDNA titre with falling C3 and C4 often heralds a flare, particularly a renal flare. ^[1]

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References13ShowHide

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2. [2]Alarcón GS, McGwin G, Bertoli AM, et al. Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L) Ann Rheum Dis, 2007.PMID 17389655
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8. [8]Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis Ann Rheum Dis, 2020.PMID 32220834
9. [9]Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases Kidney Int, 2021.PMID 34556256
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11. [11]Morand EF, Furie R, Tanaka Y, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus N Engl J Med, 2020.PMID 31851795
12. [12]Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial Lancet, 2021.PMID 33971155
13. [13]Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J Thromb Haemost, 2006.PMID 16420554